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EW NEWS & OPINION 18 October 2014 by Maxine Lipner EyeWorld Senior Contributing Writer Eyeing the ocular vitamin aisle T here was a time when vitamin supplements were not on most ophthal- mologists' radar. But that has changed, according to Eric D. Donnenfeld, MD, clinical professor of ophthalmology, New York University Medical Center. "Ophthalmic supplements have become one of the mainstays of ophthalmic practices," Dr. Donnenfeld said. Dr. Donnenfeld finds that supplementation is of importance for both ocular surface disease and macular degeneration, with omega-3 playing a pivotal role. He pointed to the Harvard Women's Health Study, which indicated that those who regularly consumed tuna fish showed a lower incidence of dry eye disease as a result. "The most important finding was that it was dose-dependent," Dr. Donnenfeld said. "It wasn't whether you ate fish or not, it was the quantity." It was also the type of fish, with those containing omega-3 heralded as the ones that were essential, he said. On the omega-3 shelf Consumption of omega-3s today is 50 times less than it was 100 years ago in the U.S., he observed. "The lack of ingestion of omega-3s has resulted in a variety of different maladies including arthritis, dry eye disease, and skin problems," he said. Unless they consume very high levels of fish, in D . Donnenfeld's view, all patients should be on omega-3 supplements. "I am a big believer and have been using oral omega-3 supplements myself for the last 10 years," he said. However, all omega-3 sup- plementation is not equal. As Dr. Donnenfeld came to realize about 1½ years ago upon meeting Jorn Dyerberg, MD, from Norway, some omega-3 is not even recognized by the human body. Dr. Dyerberg was the first to undertake studies with the Eskimos in the 1960s showing high omega-3 ingestion resulted in low incidence of cardiac disease. "In the U.S., most of the omega- 3 supplements that we ingest have alcohol added to them," Dr. Donnenfeld said. "The alcohol precipitates out the mercury—that's what makes fish oil safe." Howeve , it also converts the fish oil from a natural triglyceride to an ethyl ester, not found in nature, and this is something that many cannot metabolize. This not only results in GI distress, but also means the omega-3 is not efficiently absorbed. "What Dr. Dyerberg told me and has published is you achieve 3 times better absorption [with the natural triglyceride form], and because of the higher absorption, you get a much higher therapeutic effect," Dr. Donnenfeld said. Cynthia Matossian, MD, Ma- tossian Eye Associates, Doylestown, Pa., likewise stresses the importance of using the naturally recognized triglyceride form found in fish. " e have enzymes in our digestive tract to recognize and readily digest the triglyceride form without the unpleasant GI side effects," she said. There are currently 3 companies in the U.S. that make the re-es- terified omega-3, according to D . Donnenfeld. These include Carlson Labs (Arlington Heights, Ill.), Nordic Naturals (Watsonville, Calif.), and Physician Recommended Nutriceu- ticals (PRN/Alphaeon Corporation, Irvine, Calif.). The latter, which both Dr. Matossian and Dr. Donnenfeld recommend to their patients, is sold in physicians' offices onl , while the others are available over the counter. For dry eye patients, Dr. Matossian said the recommended dose is 4 capsules daily. However, since she has gotten pushback from some patients on this, she instead starts them out on 2 capsules and then waits 4 to 6 months. She brings patients back for an omega-3 blood index test (OmegaQuant, Sioux Falls, S.D.). After learning the patient's specific omega-3 level, she adjusts the patient's supplement intake based on their specific need A second group who may ben- efit from omega-3s are those with macular degeneration, Dr. Matossian noted. She favors supplements that include omega-3 as well as lutein and zeaxanthin. In particular this may be helpful for early AMD cases. "I know of studies coming out of Wills Eye where they evaluated the therapeutic effect of omega-3 with lutein and zeaxanthin for patients with macular drusen, a precursor to macular degeneration," Dr. Matossian said. For patients with early drusen who have a positive family history of macular degeneration, she recommends Omega Advantage (PRN). Daniel Kiernan, MD, Ophthal- mic Consultants of Long Island, Lynbrook, N.Y., a retinal specialist, also recommends supplements for his patients. With AMD becoming more prevalent as the population is living longer, supplementation is something he urges all to consider. "I would say 100% of (my) patients with macular degeneration are on supplements, as recommended by the AREDS2 study," he said. While the use of omega-3 was not found to be beneficial by AREDS2, Dr. Kiernan views the jury as "still out on this." He said that for the trial they used a low-dose, low-potency ester formulation of omega-3. "There are much higher quality triglyceride formulations now commonly available through some manufacturers that have at least 3 times the absorption of the ester formulation," he said, adding it was also recognized that higher doses must be absorbed to have an anti-inflammato y effect. "I still recommend omega-3 supplements to macular degeneration patients as well as other patients such as diabetics," he said. For the glaucoma cart Those with glaucoma may also ben- efit from supplement use, according to Robert Ritch, MD, Shelley and Steven Einhorn Distinguished Chair, professor of ophthalmology, New York Eye and Ear Infirma y. For his normal tension glaucoma patients in particular, he routinely recommends the use of ginkgo biloba extract (GBE). He finds it can increase ocular blood flow and antioxidant activit , among other benefits. He initially stumbled on GBE in 1996, when he read an article about it. "I said, 'This has everything we need for glaucoma—it inhibits lipid peroxidation, it preserves mitochondrial structure and func- tion, it prevents against mitochon- drial aging changes, and preserves mitochondrial ATP production.'" In addition, GBE improves blood flow to the eye and the brain, he noted. He recommends the spice curcumin for many of his cataract, macular degeneration, and glauco- ma patients. He has also found it to be useful for pre-granular exfoliation syndrome, which he had in one of his own eyes. "On dilation my pressure went up to 24, and I had pigment release into the anterior chamber," he said. "The only thing I did differently is I started taking curcumin just by happenstance." He soon found that the pre- granular exfoliation disappeared. "I don't get a pressure rise or pigment liberation on dilation anymore," he said, adding that the same was true for 4 patients of his using the same spice. However, curcumin does not appear to help in cases involving mature exfoliation fibers, he noted Alpha lipoic acid may also prove helpful for glaucoma patients, he said. Taken orally, it has been shown to increase antioxidant gene and protein expression and also improve protection of retinal ganglion cells, Dr. Ritch said. In addition, when given topically after trabeculectomy, it has been shown to improve bleb function in rabbits. He also touts the value of ome- ga-3 because it has been associated with cardiovascular, cerebrovascular, and glaucoma protection. In the future, Dr. Donnenfeld thinks nutritional supplements will become even more popular in ophthalmology. "These have become more popular over the last 5 to 10 years and are still in their growth phase," he said. "I think they will become primary therapy for most patients with many ocular conditions as we learn that the use of nutritional supplements can either prevent or reverse the damage done by the poor nutrition that we have here in the United States." EW Editors' note: Dr. Donnenfeld has financial interests with Alcon (Fort Worth, Texas), Bausch + Lomb (Bridgewater, N.J.), and Alphaeon/PRN. Dr. Kiernan has financial interests with Alphaeon/PRN. Dr. Matossian has financial interests with Alphaeon PRN. Dr. Ritch has no related financial interests. Contact information Donnenfeld: ericdonnenfeld@gmail.com Kiernan: danielkiernan714@yahoo.com Matossian: cmatossian@matossianeye.com Ritch: ritchmd@earthlink.net Pharmaceutical focus